Quality control of translation on the ribosome

核糖体翻译的质量控制

• 批准号: 73335919
• 负责人: Professorin Dr. Marina V. Rodnina
• 金额: --
• 依托单位: B.P. Konstantinova Petersburg Nuclear Physics Institute
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/73335919?language=en
• 关键词: Quality; control; translation; ribosome

The scope of the present proposal is to acquire quantitative understanding of quality control mechanisms of translation initiation and elongation in bacteria. Kinetic mechanisms of both reactions will be studied, monitoring fluorescence signals, including FRET, of labels introduced into components of the translation machinery. Control steps in translation initiation will be identified, and the mechanisms by which the differences in the translation initiation region of mRNAs are recognized by the initiation machinery will be investigated. Another aim is to understand the high fidelity of protein synthesis during elongation using a systems-biology approach. The kinetics of reactions that govern acceptance or rejection of aminacyl-tRNA (aa-tRNA) substrates will be measured on cognate and near-cognate codons in the absence and presence of competitor aa-tRNA. A mathematical competition model will be built to make testable predictions as to how the fidelity of protein synthesis changes with the physiological state of the cell. Finally, we plan to study the mechanism of programmed -1 frameshifting. The timing of ribosome pausing and the step at which frameshifting takes place will be determined. We will test whether one or two tRNAs are involved in frameshifting, and whether EF-G has to be present on the ribosome during slippage.

本提案的范围是获得细菌翻译起始和延伸的质量控制机制的定量理解。这两个反应的动力学机制将被研究，监测荧光信号，包括FRET，标签引入翻译机器的组成部分。将确定翻译起始的控制步骤，并研究mrna翻译起始区域的差异被起始机制识别的机制。另一个目的是了解高保真蛋白合成期间使用系统生物学方法。控制氨基基trna （aa-tRNA）底物接受或排斥反应的动力学将在同源和近同源密码子上测量，在没有和存在竞争对手aa-tRNA的情况下。将建立一个数学竞争模型，对蛋白质合成的保真度如何随着细胞的生理状态而变化做出可测试的预测。最后，我们计划研究程序-1移帧的机制。核糖体暂停的时间和帧移发生的步骤将被确定。我们将测试是否有一个或两个trna参与移帧，以及在滑动期间EF-G是否必须存在于核糖体上。

项目成果

Real-time assembly landscape of bacterial 30S translation initiation complex

• DOI: 10.1038/nsmb.2285
• 发表时间: 2012-06-01
• 期刊: NATURE STRUCTURAL & MOLECULAR BIOLOGY
• 影响因子: 16.8
• 作者: Milon, Pohl;Maracci, Cristina;Rodnina, Marina V.
• 通讯作者: Rodnina, Marina V.

tRNA tKUUU, tQUUG, and tEUUC wobble position modifications fine-tune protein translation by promoting ribosome A-site binding

• DOI: 10.1073/pnas.1300781110
• 发表时间: 2013-07-23
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Rezgui, Vanessa Anissa Nathalie;Tyagi, Kshitiz;Pedrioli, Patrick G. A.
• 通讯作者: Pedrioli, Patrick G. A.

High-efficiency translational bypassing of non-coding nucleotides specified by mRNA structure and nascent peptide

• DOI: 10.1038/ncomms5459
• 发表时间: 2014-07-01
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Samatova, Ekaterina;Konevega, Andrey L.;Rodnina, Marina V.
• 通讯作者: Rodnina, Marina V.